Coronary artery disease, in which the arteries feeding the heart narrow over time, can lead to any of a number of cardiac dysfunctions. If the narrowing prevents the heart muscle from receiving the amount of blood that it needs, a condition known as myocardial ischemia exists. Ischemia can occur during exercise, when the heart muscle's oxygen demand is greatest, or it may occur at rest. If allowed to persist, ischemia leads to heart muscle death. The primary symptom of ischemia is chest pain, or angina, although more than a third of ischemia sufferers may not experience this classic symptom (a condition known as silent ischemia).
Another cause of ischemia is myocardial infarction (MI), which occurs when an artery feeding the heart suddenly becomes blocked. This leads to acute ischemia (as opposed to the chronic ischemia usually associated with the more slow-acting processes of coronary artery disease). If left untreated, ischemia leads to myocardial cell death, or necrosis.
When an infarction is diagnosed, possible therapies include interventional catheterization (including angioplasty and/or stenting to mechanically reopen the blocked vessel) and administration of thrombolytic drugs (such as streptokinase, urokinase, or TPA). If therapy is initiated within the first thirty minutes after an MI, 100% of the myocardium can be saved. After thirty minutes, the proportion of salvageable myocardium decreases rapidly. Treatment within the first 70 minutes has also been associated with a significant decrease in in-hospital mortality.
One important component of the delay between onset of ischemia and treatment is the delay from the patient's initial symptoms until the time that he or she seeks medical assistance. In one retrospective study of heart attack survivors, only 25% contacted medical help within the first hour after onset of symptoms; 40% waited more than four hours. These patients delayed primarily because they believed that symptoms would go away or that the symptoms were not serious. Another important group of MI sufferers is the 33% (according to one study) who do not experience the classic symptom of chest pain. These patients are less likely to seek medical attention, and if they do, they may be treated less aggressively.
A large number of acute-MI patients have had previous hospitalizations for heart-related problems. Conversely, a significant number of patients who undergo catheterizations as a result of an MI will have a recurrent event within one year. As many as half of intracardiac defibrillator (ICD) recipients will have an MI within 5 years of its implantation.
The tissue death associated with infarction can lead to a number of other heart dysfunctions. If the infarction causes a disruption in the electrical conduction pathway of the heart (used to initiate its muscular contraction), then various heart rhythm abnormalities, or arrhythmias, can result. These arrhythmias can be fatal if they are not corrected quickly, so implantable therapies such as ICDs are often used to continuously monitor and treat these patients. These solutions place leads in some subset of the ventricle, atrium, or cardiac veins in order to sense and distribute electrical energy in the right atrium and both ventricles.
If the infarction reduces the pumping ability of the heart, then the heart may remodel to compensate; this remodeling can lead to a degenerative state known as heart failure. Heart failure can also be precipitated by other factors, including valvular heart disease and cardiomyopathy. Pumping ability is usually indicated by a reduced ejection fraction, the percentage of the ventricle's full volume that is delivered to the body in a single cycle. Treatment of reduced pumping ability can be pharmacologic, or ventricular assist devices (VADs) can be implanted for pumping support. In certain cases, heart transplantation may be used to repair an ailing heart.
When patients arrive at the hospital with symptoms consistent with heart disease, they may undergo any of a number of conventional diagnostic tests. The lack of accuracy of these tests, and the time required for their use, further contribute to the total time between the onset of symptoms and the initiation of therapy. These tests can be broken into four broad categories based on the type of parameter measured: chemical, hemodynamic, electrical, or mechanical.
Chemical tests measure biochemical markers in the patient's bloodstream that appear or change in concentration preferentially after myocardial cell death. Examples of such markers include creatine kinase, CK-MB, lactate dehydrogenase (LDH), troponin I & T, and myoglobin. These markers are useful in the diagnosis of acute MI because they begin to rise in concentration three to six hours after ischemia begins, and fall back to baseline values within a few days.
Hemodynamic testing involves the determination of local blood flow or pressure in the heart's chambers and vessels. Changes in chamber pressure waveforms over the cardiac cycle can indicate valvular dysfunction or heart failure. These measurements are typically made by inserting a catheter into the location to be monitored.
Electrical testing involves some measurement of the electrical conduction within the heart, typically accomplished with an electrocardiogram (EKG). EKGs are typically collected through a number of patch electrodes attached to the patient's skin. Many heart dysfunctions manifest themselves on the EKG, though some cause more subtle changes than others. Arrhythmias can be diagnosed on the EKG, as long as the EKG equipment recorded the arrhythmic event. Various changes in the EKG pattern can indicate different stages and degrees of infarction. For example, elevation or depression in the ST segment of the waveform is often associated with acute ischemia (present in the early stages of acute myocardial infarction). EKG recording from a number of electrodes placed at various locations on the body can be used to localize the region of ischemic muscle. Trained hospital personnel typically read and diagnose EKGs, though technology exists for automated detection of some problems.
Mechanical cardiac tests include wall-motion assessment using echocardiography (i.e., diagnostic ultrasound) or MRI or CT. Contractility, and therefore overall motion, of the heart wall changes significantly during acute and chronic ischemia. These changes can be visualized (and localized) using any of these imaging modalities. Exercise-induced ischemia can be visualized by performing these tests both before and after exercise. Functional assessment can also be done with these imaging modalities by calculating ejection fraction and other functional parameters from the acquired images.
Such conventional tests of heart function have several shortcomings. Continuous ambulatory monitoring with these devices is not practical. Although ambulatory EKG monitors (known as Holter or event monitors) can be used, they are typically not well tolerated for more than 24 hours at a time. Electrical abnormalities are not apparent in a large number of patients suffering from acute coronary events, including a significant population of patients with so-called non-ST-elevated MI. Also, these monitors require some expert diagnosis, reducing their desirability outside of the hospital. Finally, the external nature of these diagnostic tools reduces their sensitivity and ability to localize events to a specific region within the heart.
In an attempt to address these issues, technologies have been proposed for implantable ischemia detection through electrodes placed within the ventricle or chest cavity, to monitor electrograms within the heart. These devices may use an automated processing algorithm for determining whether ischemia is present based on the recorded electrograms, and are typically placed along an electrical lead placed in the atria or ventricles. Other proposed implantable devices measure biochemical markers for ischemia. Chemical sensors for this purpose are sometimes deployed in coronary arteries for local ischemia detection. Upon detection of an event, these implantable devices can alert the patient of danger or deliver early therapy.
However, these technologies have significant shortcomings in the early diagnosis of myocardial ischemia and other cardiac dysfunction. In particular, techniques are used that have a low sensitivity to early ischemic events. In the case of electrogram recording, there is a reliance on measurements that can return to baseline rapidly after reperfusion, making diagnosis of transient events or stunned myocardium difficult. In addition, electrical signals are susceptible to interference from other implanted devices, including electrical pacing and defibrillation pulses. Certain biochemical analyses (such as CK-MB) measure events that occur hours after the onset of ischemia.
Coronary heart disease (CHD) is the leading cause of death in the United States for both men and women. The importance of this disease, and the significant deficiencies in current diagnostic methods, make improvement in detection highly desirable. The present invention addresses these issues.